To document virus-induced diabetes in a species close to man which could be studied longitudinally, we inoculated rhesus monkeys with the virulent Trinidad strain of Venezuelan Encephalitis Virus (V.E.). There followed a progressive impairment in glucose tolerance and serum insulin levels (fasting and following glucose-stimulation) over a 5 month period. This significant decrease in fasting insulin levels was accompanied by a much smaller decrease in plasma glucagon levels at 5 mo. such that the IRI/IRG molar ratio was considerably decreased at ths time. The control fasting IRI/IRG was 2-4 in contrast to the 5 mo. fasting IRI/IRG value of 0.6 (p 0.05). Cortisol values were within the normal range during each GTT. The data show a progressive impairment in glucose tolerance as well as basal and glucose stimulateed IRI levels in monkeys over a 5 mo. period. These and longer term studies provide the first primate model for investigating the evolution of carbohydrate abnormalities and possible complication thereof following a viral infection. When C57 KSJ mice heterozygous (Db/plus) or homozygous (Db/Db) for diabetes were inoculated with TC-83 strain of V.E., both groups of mice demonstrated significantly lower serum insulin levels following infection although glucose tolerance in these same mice did not change appreciably.